The present invention relates to aminoketone derivatives and physiologically-acceptable salts thereof, which have muscle relaxant effects, and therapeutic agents containing them as effective ingredients. The aminoketone derivatives and the physiologically-acceptable salts thereof are useful as effective ingredients of centrally acting muscle relaxants employed for the treatment of diseases featuring spastic paralysis as a principal symptom, dolorous muscle spasticity caused by motor organ diseases, and the like; and as effective ingredients for the improvement of pollakiurea caused by neurogenic bladders or unstable bladders.
The present invention relates to optically active 3-phenyl-5-[2-(1-pyrrolidinylmethyl)butyryl]isoxazole having a centrally acting muscle relaxant action and a method for preparing the same.
2. Description of the Related Art
Some aminoketone derivatives having centrally acting muscle relaxant effects have been known to date, including tolperisone hydrochloride and eperisone hydrochloride, both clinically used these days and in addition, the compounds disclosed for example in Japanese Patent Application Laid-Open No. 39816/1988 and European Patent Publication No. 163537. Similarly to tolperisone hydrochloride and eperisone hydrochloride, the compounds disclosed in these publications all have an aromatic hydrocarbon moiety bonded to an aminoketone moiety. Further, European Patent Publication No, 273375 discloses to the effect that aminoketone derivatives having a similar structure are effective for the improvement of pollakiurea.
Tolperisone hydrochloride and eperisone hydrochloride referred to above are however not fully satisfactory as centrally acting muscle relaxants from the standpoints of strength of action, prolonged action and freedom from side effects (central depressant effects), although they are widely used for diseases featuring spastic paralysis as a principal symptom.
Heretofore, with regard to the optical resolution process of a compound having a centrally acting muscle relaxant action, techniques using an optical resolving agent are known. For example, Japanese Patent Application Laid-open No. 40779/1978 discloses a technique which comprises converting dl-tolperisone into two kinds of diastereomer salts by the use of optically active acetylphenylglycine as the resolving agent, separating these diastereomer salts mutually by the utilization of a difference of solubility thereof, and then recovering optically active tolperisone. In addition, Japanese Patent Application Laid-open Nos. 225367/1988 and 131171/1989 disclose a technique which comprises separating dl-2-methyl-l-(4-trifluoromethylphenyl)-3-pyrrolidino-l-propane by the use of optically active acetylphenylglycine or optically active malic acid as the resolving agent, and then isolating optically active 2-methyl-l-(4-trifluoromethylphenyl)-3-pyrrolidino-1-propane.